Never let it go: Stopping key mechanisms underlying metastasis to fight pancreatic cancer

E. Giovannetti, C. L. van der Borden, A. E. Frampton, A. Ali, O. Firuzi, G. J. Peters

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive neoplasm, predicted to become the second leading cause of cancer-related deaths before 2030. This dismal trend is mainly due to lack of effective treatments against its metastatic behavior. Therefore, a better understanding of the key mechanisms underlying metastasis should provide new opportunities for therapeutic purposes. Genomic analyses revealed that aberrations that fuel PDAC tumorigenesis and progression, such as SMAD4 loss, are also implicated in metastasis. Recently, microRNAs have been shown to play a regulatory role in the metastatic behavior of many tumors, including PDAC. In particular, miR-10 and miR-21 have appeared as master regulators of the metastatic program, while members of the miR-200 family are involved in the epithelial-to-mesenchymal switch, favoring cell migration and invasiveness. Several studies have also found a close relationship between cancer stem cells (CSCs) and biological features of metastasis, and the CSC markers ALDH1, ABCG2 and c-Met are expressed at high levels in metastatic PDAC cells. Emerging evidence reveals that exosomes are involved in the modulation of the tumor microenvironment and can initiate PDAC pre-metastatic niche formation in the liver and lungs. In this review, we provide an overview of the role of all these pivotal factors in the metastatic behavior of PDAC, and discuss their potential exploitation in the clinic to improve current therapeutics and identify new drug targets.

Original languageEnglish
Pages (from-to)43-59
Number of pages17
JournalSeminars in Cancer Biology
Volume44
DOIs
Publication statusPublished - 1 Jun 2017

Cite this

Giovannetti, E. ; van der Borden, C. L. ; Frampton, A. E. ; Ali, A. ; Firuzi, O. ; Peters, G. J. / Never let it go : Stopping key mechanisms underlying metastasis to fight pancreatic cancer. In: Seminars in Cancer Biology. 2017 ; Vol. 44. pp. 43-59.
@article{f041b18277384167b722086eda2f44fe,
title = "Never let it go: Stopping key mechanisms underlying metastasis to fight pancreatic cancer",
abstract = "Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive neoplasm, predicted to become the second leading cause of cancer-related deaths before 2030. This dismal trend is mainly due to lack of effective treatments against its metastatic behavior. Therefore, a better understanding of the key mechanisms underlying metastasis should provide new opportunities for therapeutic purposes. Genomic analyses revealed that aberrations that fuel PDAC tumorigenesis and progression, such as SMAD4 loss, are also implicated in metastasis. Recently, microRNAs have been shown to play a regulatory role in the metastatic behavior of many tumors, including PDAC. In particular, miR-10 and miR-21 have appeared as master regulators of the metastatic program, while members of the miR-200 family are involved in the epithelial-to-mesenchymal switch, favoring cell migration and invasiveness. Several studies have also found a close relationship between cancer stem cells (CSCs) and biological features of metastasis, and the CSC markers ALDH1, ABCG2 and c-Met are expressed at high levels in metastatic PDAC cells. Emerging evidence reveals that exosomes are involved in the modulation of the tumor microenvironment and can initiate PDAC pre-metastatic niche formation in the liver and lungs. In this review, we provide an overview of the role of all these pivotal factors in the metastatic behavior of PDAC, and discuss their potential exploitation in the clinic to improve current therapeutics and identify new drug targets.",
keywords = "Cancer stem cells, Exosomes, Metastasis, microRNAs, Novel therapeutics, Pancreatic cancer",
author = "E. Giovannetti and {van der Borden}, {C. L.} and Frampton, {A. E.} and A. Ali and O. Firuzi and Peters, {G. J.}",
year = "2017",
month = "6",
day = "1",
doi = "10.1016/j.semcancer.2017.04.006",
language = "English",
volume = "44",
pages = "43--59",
journal = "Seminars in Cancer Biology",
issn = "1044-579X",
publisher = "Academic Press Inc.",

}

Never let it go : Stopping key mechanisms underlying metastasis to fight pancreatic cancer. / Giovannetti, E.; van der Borden, C. L.; Frampton, A. E.; Ali, A.; Firuzi, O.; Peters, G. J.

In: Seminars in Cancer Biology, Vol. 44, 01.06.2017, p. 43-59.

Research output: Contribution to journalReview articleAcademicpeer-review

TY - JOUR

T1 - Never let it go

T2 - Stopping key mechanisms underlying metastasis to fight pancreatic cancer

AU - Giovannetti, E.

AU - van der Borden, C. L.

AU - Frampton, A. E.

AU - Ali, A.

AU - Firuzi, O.

AU - Peters, G. J.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive neoplasm, predicted to become the second leading cause of cancer-related deaths before 2030. This dismal trend is mainly due to lack of effective treatments against its metastatic behavior. Therefore, a better understanding of the key mechanisms underlying metastasis should provide new opportunities for therapeutic purposes. Genomic analyses revealed that aberrations that fuel PDAC tumorigenesis and progression, such as SMAD4 loss, are also implicated in metastasis. Recently, microRNAs have been shown to play a regulatory role in the metastatic behavior of many tumors, including PDAC. In particular, miR-10 and miR-21 have appeared as master regulators of the metastatic program, while members of the miR-200 family are involved in the epithelial-to-mesenchymal switch, favoring cell migration and invasiveness. Several studies have also found a close relationship between cancer stem cells (CSCs) and biological features of metastasis, and the CSC markers ALDH1, ABCG2 and c-Met are expressed at high levels in metastatic PDAC cells. Emerging evidence reveals that exosomes are involved in the modulation of the tumor microenvironment and can initiate PDAC pre-metastatic niche formation in the liver and lungs. In this review, we provide an overview of the role of all these pivotal factors in the metastatic behavior of PDAC, and discuss their potential exploitation in the clinic to improve current therapeutics and identify new drug targets.

AB - Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive neoplasm, predicted to become the second leading cause of cancer-related deaths before 2030. This dismal trend is mainly due to lack of effective treatments against its metastatic behavior. Therefore, a better understanding of the key mechanisms underlying metastasis should provide new opportunities for therapeutic purposes. Genomic analyses revealed that aberrations that fuel PDAC tumorigenesis and progression, such as SMAD4 loss, are also implicated in metastasis. Recently, microRNAs have been shown to play a regulatory role in the metastatic behavior of many tumors, including PDAC. In particular, miR-10 and miR-21 have appeared as master regulators of the metastatic program, while members of the miR-200 family are involved in the epithelial-to-mesenchymal switch, favoring cell migration and invasiveness. Several studies have also found a close relationship between cancer stem cells (CSCs) and biological features of metastasis, and the CSC markers ALDH1, ABCG2 and c-Met are expressed at high levels in metastatic PDAC cells. Emerging evidence reveals that exosomes are involved in the modulation of the tumor microenvironment and can initiate PDAC pre-metastatic niche formation in the liver and lungs. In this review, we provide an overview of the role of all these pivotal factors in the metastatic behavior of PDAC, and discuss their potential exploitation in the clinic to improve current therapeutics and identify new drug targets.

KW - Cancer stem cells

KW - Exosomes

KW - Metastasis

KW - microRNAs

KW - Novel therapeutics

KW - Pancreatic cancer

UR - http://www.scopus.com/inward/record.url?scp=85018396034&partnerID=8YFLogxK

U2 - 10.1016/j.semcancer.2017.04.006

DO - 10.1016/j.semcancer.2017.04.006

M3 - Review article

VL - 44

SP - 43

EP - 59

JO - Seminars in Cancer Biology

JF - Seminars in Cancer Biology

SN - 1044-579X

ER -